G. Gregoire et al., ACTIVATION OF VOLTAGE-INDEPENDENT CA2+ ENTRY BY NORADRENALINE INVOLVES CGMP IN VASCULAR MYOCYTES, Cell calcium, 18(6), 1995, pp. 505-514
Stimulation of portal vein myocytes with noradrenaline (NA) in the pre
sence of a voltage-dependent Ca2+ channel blocker, evoked a transient
increase in the concentration of free cytosolic Ca2+, due to inositol
1,4,8-trisphosphate mediated Ca2+ release, followed by activation of a
Ca2+ entry pathway, Combining patch-clamp and Indo-1 measurements we
have tested the effects of various pharmacological agents on this Ca2 entry following NA-induced Ca2+ release in order to determine the mec
hanism involved, Only the guanylate cyclase inhibitor LY-83583 specifi
cally inhibited the maintained Ca2+ entry during NA stimulation, This
inhibition was reversed by dibutyryl cGMP (DB-cGMP) or 8-bromo cGMP, U
nder control conditions, addition of DB-cGMP to the external solution
was without effect, Thapsigargin and caffeine each depleted the intrac
ellular Ca2+ store but did not evoke Ca2+ entry in venous myocytes und
er control conditions, However, application of DB-cGMP or NA after Ca2
+ store depletion induced by caffeine or thapsigargin caused a rise in
[Ca2+](i) by activation of a Ca2+ entry pathway. The effect of cGMP s
eems to involve phosphorylation since cGMP-activated protein kinase in
hibitors KT-5823 and H-8 blocked the NA-induced Ca2+ entry, Our result
s thus suggest that the activation of the voltage-independent Ca2+ ent
ry by NA involves an increase in cellular cGMP.